Abstract

3,4-methylenedioxymethamphetamine (MDMA) users have impaired verbal memory, and voxel-based morphometry has shown decreased grey matter in Brodmann area (BA) 18, 21 and 45. Because these regions play a role in verbal memory, we hypothesized that MDMA users would show altered brain activation in these areas during performance of a functional magnetic resonance imaging (fMRI) task that probed semantic verbal memory. Polysubstance users enriched for MDMA exposure participated in a semantic memory encoding and recognition fMRI task that activated left BA 9, 18, 21/22 and 45. Primary outcomes were percent blood oxygen level-dependent signal change in left BA 9, 18, 21/22 and 45, accuracy and response time. During semantic recognition, lifetime MDMA use was associated with decreased activation in left BA 9, 18 and 21/22 but not 45. This was partly influenced by contributions from cannabis and cocaine use. MDMA exposure was not associated with accuracy or response time during the semantic recognition task. During semantic recognition, MDMA exposure was associated with reduced regional brain activation in regions mediating verbal memory. These findings partially overlap with previous structural evidence for reduced grey matter in MDMA users and may, in part, explain the consistent verbal memory impairments observed in other studies of MDMA users.